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Background. This work used bioinformatic analysis to identify the relationship between periodontitis (PD) and aging, which could lead to new treatments for periodontal disease in the elderly. Method. Four microarray datasets were obtained from the Gene Expression Omnibus (GEO) database and analyzed in R language to identify differentially expressed genes (DEGs). The common DEGs of PD and aging were evaluated as key genes in this investigation by a Venn diagram. These common DEGs were analyzed through additional experiments and analysis, such as pathway analysis and enrichment analysis, and a network of protein-protein interactions (PPIs) was constructed. Cytoscape was used to visualize hub genes and critical modules based on the PPI network. Interaction of TF-genes and miRNAs with hub genes is identified. Result. 84 common DEGs were found between PD and aging. Cytohubba was performed on the PPI network obtained from STRING tool, and the top 10 genes (MMP2, PDGFRB, CTGF, CD34, CXCL12, VIM, IL2RG, ACTA2, COL4A2, and TAGLN) were selected as hub genes. VIM may be a potential biomarker in the analysis of linked hub gene regulatory networks, and hsa-mir-21 and hsa-mir-125b are predicted to be associated in PD and aging. Conclusion. This study investigated the key genes and pathways interactions between PD and aging, which may help reveal the correlation between PD and aging. The current research results are obtained by prediction, and follow-up biological experiments are required for further verification. [ABSTRACT FROM AUTHOR]

Objective. To explore the potential biological roles of long noncoding RNA (lncRNA) RNCR3 in human hepatocellular carcinoma (HCC). Methods. First, the expression of RNCR3 was detected by qRT-PCR. Then, in vitro experiments were performed to investigate the effects of RNCR3 on the proliferation, cell cycle, migration, and invasion of HCC cells, while the effects of RNCR3 on HCC tumor growth and metastasis were investigated using in vivo experiments. Finally, western blot was used to study the activation of the Akt/GSK3β signaling pathway. Results. RNCR3 was highly expressed in both HCC tissues and cells, and the expression of RNCR3 was closely related to tumor size, tumor number, TNM stage, and overall survival time. In vitro, RNCR3 served as an oncogene to promote cell proliferation, migration, and invasion, and in vivo, RNCR3 promoted the growth and metastasis of HCC tumors. In terms of mechanism, RNCR3 induced the phosphorylation of Akt (thr308 and ser473) and GSK3β (ser9) but decreased the expression of GSK3β, which activated the Akt/GSK3β signaling pathway. Conclusion. The high expression of lncRNA RNCR3 in HCC can promote the proliferation, migration, invasion, growth, and metastasis of HCC by activating the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Chronic inflammation is considered to be the cause of ovarian dysfunction. Increasing evidence in animal studies and in preliminary clinical trials has demonstrated that MSCs possess immunomodulatory effects via their interaction with immune cells. However, their contribution to PCOS remains unclear. In this study, we showed that the administration of hUC-MSCs could efficiently improve the pathological changes of PCOS mice induced by dehydroepiandrosterone (DHEA), including ovarian histopathology and function. Moreover, we found that the administration of MSCs significantly downregulated the expression of proinflammatory factors (TNF-α, IL-1β, and IFN-γ) and fibrosis-related genes (CTGF) in ovarian and uterus tissues and affected the systemic inflammatory response. The percentage of peripheral neutrophils, M1 macrophages, and B cells was significantly reduced, while M2 macrophages and regulatory T cells (Tregs) were increased in hUC-MSC-treated mice. In the spleen, the percentage of neutrophils, M1 macrophages, IFN-γ+CD19+B cell, IFN-γ+CD4+T cells (Th1), and IL-17+CD4+T cells (Th17) was significantly decreased in hUC-MSC-treated mice. These results suggested that hUC-MSC treatment could alleviate ovarian dysfunction by inhibiting ovarian local and systemic inflammatory responses. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the alterations in macrophage polarization in patients with endometriosis as well as the underlying molecular mechanisms.Methods: Peritoneal washings, serum samples, and endometrial tissues were collected from endometriosis patients and control subjects. Endometrial stromal cells (ESCs) were isolated from endometrial tissue, and conditioned medium was prepared by treating ESCs with or without various concentrations of interleukin- (IL-) 6, estrogen, or progestin. The frequencies of CD86+ and CD163+ cells and expression levels of these markers as well as the cytokines IL-12 and IL-10 were measured in THP-1- (human monocytic leukemia cell) derived macrophages.Results: There was a decrease in the percentage of CD86+ macrophages in the peritoneal wash solution of patients with endometriosis. Ectopic endometrial homogenates could promote M1 to M2 macrophage polarization in response to lipopolysaccharide (LPS), as evidenced by the increased percentage of CD163+ macrophages and increased IL-10 expression as well as a decreased percentage of CD86+ cells and lower IL-12 expression. In contrast, addition of serum from women with endometriosis to THP-1 cells resulted in the polarization of macrophages towards both M1 and M2 phenotypes. Upregulation of Smad2/Smad3 in macrophages upon exposure to eutopic and ectopic endometrial homogenates as well as serum of women with endometriosis was observed, and blockage of Smad2/Smad3 with their inhibitor SB431542 could reverse the macrophage polarization from M1 to M2. Conditioned medium induced by IL-6, but neither estrogen nor progestin, could facilitate M2 polarization. Neutralization of IL-6 diminished macrophage M2 polarization in endometriosis.Conclusion: This study provides detailed evidence supporting alterations in M1 to M2 macrophage polarization that may contribute to the initiation as well as progression of endometriosis. [ABSTRACT FROM AUTHOR]

Abnormal immune response of the body against substances and tissues causes autoimmune diseases, such as polymyositis, dermatomyositis, and rheumatoid arthritis. Irregular lipid metabolism and inflammation may be a significant cause of autoimmune diseases. Although much progress has been made, mechanisms of initiation and proceeding of metabolic and inflammatory regulation in autoimmune disease have not been well-defined. And novel markers for the detection and therapy of autoimmune disease are urgent. mTOR signaling is a central regulator of extracellular metabolic and inflammatory processes, while DEP domain-containing mTOR-interacting protein (DEPTOR) is a natural inhibitor of mTOR. Here, we report that overexpression of DEPTOR reduces mTORC1 activity in lymphocytes of human peripheral blood mononuclear cells (PBMCs). Combination of DEPTOR overexpression and mTORC2/AKT inhibitors effectively inhibits lipogenesis and inflammation in lymphocytes of PBMC culture. Moreover, DEPTOR knockdown activates mTORC1 and increases lipogenesis and inflammations. Our findings provide a deep insight into the relationship between lipid metabolism and inflammations via DEPTOR-mTOR pathway and imply that DEPTOR-mTOR in lymphocytes of PBMC culture has the potential to be as biomarkers for the detection and therapies of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective. This study explored the effect of different nutritional nursing support on nutritional status, immune function, postoperative bowel motility, and complications in elderly patients with gastrointestinal tumors during the perioperative period. Methods. 300 patients with gastrointestinal tumors treated in the Department of Gastroenterology and anorectal surgery of Hangzhou First People's Hospital Affiliated with the Medical College of Zhejiang University from February 2018 to March 2020 were selected as the research objects in this study. Patients were divided into the early enteral nutrition (EEN) and total parenteral nutrition (TPN) groups (150 cases in each group) according to the principle of odd and even admission numbers. The patients in the EEN and TPN groups were given enteral nutrition nursing support and parenteral nutrition nursing support, respectively. The nutritional status, immune function, postoperative bowel motility, and complication rate of the two groups were evaluated 7 days after the operation. Results. The nutritional indexes decreased 3 days after the operation and gradually recovered 7 days after the operation in both groups with different nutritional nursing support. The Hb, TRF, PAB, and ALB indexes in the TPN group were significantly lower than those in the EEN group (P < 0.01). On the 7th day after the operation, the indexes of peripheral blood immunoglobulin (IgG, IgM, and IgA) were significantly lower than those in the TPN group, and T lymphocyte subsets (CD4, CD8, and CD4/CD8) demonstrated that the immunological indexes of patients in the EEN group were significantly higher than those in the TPN group (P < 0.01). In terms of intestinal peristalsis, the time of first exhaust and first defecation in the EEN group was significantly shorter than that in the TPN group (P < 0.01) during the perioperative period. Furthermore, both groups had different degrees of complications, while patients demonstrated a lower complication rate in the EEN group compared to those in the TPN group, suggesting a safer postoperative mode. The results of subgroup analysis showed that the nutritional indexes of the gastric cancer group 7 days after operation were significantly higher than those of the colorectal cancer group under EEN and TPN nutritional support modes. Conclusion. Clinical results have suggested that enteral nutrition nursing support can improve the perioperative nutritional status of elderly patients with gastrointestinal tumors by enhancing the immune function and promoting intestinal peristalsis. Meanwhile, the postoperative EEN mode reduces the rate of complications and demonstrates higher safety. Therefore, it has a high clinical application value. [ABSTRACT FROM AUTHOR]

The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) have been proposed to be involved in some autoimmune diseases and have been successfully tested in patients and mice. But their contribution to psoriasis and the underlying mechanisms involved remains elusive. Here, we explored the feasibility of using human umbilical cord-derived MSC (hUC-MSC) infusion as a therapeutic approach in an imiquimod- (IMQ-) induced psoriasis mouse model. MSC infusion were found to significantly reduce the severity and development of psoriasis, inhibit the infiltration of immune cells to the skin, and downregulate the expression of several proinflammatory cytokines and chemokines. Our results provide an explanation for the therapeutic effects of MSC infusion by first suppressing neutrophil function and then downregulating the production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs). Therefore, we discovered a novel mechanism of stem cell therapy for psoriasis. In summary, our results showed that MSC infusion could be an effective and safe treatment for psoriasis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate growth factors release kinetics for the combination of fresh platelet-rich fibrin (F-PRF) and lyophilized PRF (L-PRF) with different ratios to promote bone tissue regeneration. First, we quantified the level of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-AB (PDGF-AB) in vitro and analyzed their release kinetics from F-PRF, L-PRF, and the fresh/lyophilized PRF in different weight ratios (F:L=1:1, 1:3, 1:5). The second experimental phase was to investigate the proliferation and differentiation of bone mesenchymal stem cells (BMSCs) as a functional response to the factors released. To further test the osteogenic potential in vivo, different scaffolds (F-PRF, or L-PRF, or F:L=1:1) were implanted in rabbit cranial bone defects. There was a statistically significant increase in proliferation and differentiation of BMSCs when the culture medium contained different PRF exudates collected at day 14 compared with the negative control group. The results showed that the new bone formation in the fresh/lyophilized PRF (1:1) was much more than that of other groups in defects at both 6 and 12 weeks. Our data suggested growth factor concentration and release kinetics as a consequence of fresh and lyophilized PRF combination, which is an effective way for promoting bone regeneration. [ABSTRACT FROM AUTHOR]

Mobile roaming authentication scheme achieves the mutual authentication and session key establishment between the mobile user and the foreign agent. In 2013, Xie et al. pointed out that Chen et al.'s scheme is vulnerable to offline password attack, and does not achieve fair session key generation, user untraceability, user friendliness, and perfect forward secrecy, and then they proposed an improved scheme. In this paper, we propose an improvement of Xie et al.'s scheme, since the foreign agent may confuse the mobile users when multiple mobile users simultaneously access the foreign agent in Xie et al.'s scheme. Further, we prove the formal security of the proposed scheme, and present the performance comparison between our scheme and some related schemes. The proposed scheme is more efficient and secure than other related schemes and is suitable for using in the global mobility network. [ABSTRACT FROM AUTHOR]

Background. The impaired osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a major cause of bone remodeling imbalance and osteoporosis. The bicaudal C homologue 1 (BICC1) gene is a genetic regulator of bone mineral density (BMD) and promotes osteoblast differentiation. The purpose of this study is to explore the probable function of BICC1 in osteoporosis and osteogenic differentiation of aged BMSCs. Methods. We examined the GSE116925 microarray dataset obtained from the Gene Expression Omnibus (GEO) database. The GEO2R algorithm identified differentially expressed genes (DEGs) in Sca-1+ BMSCs from young (3 months old) and old (18 months old) mice. Then, to identify the most crucial genes, we used pathway enrichment analysis and a protein-protein interaction (PPI) network. Furthermore, starBase v2.0 was used to generate the regulatory networks between BICC1 and related competing endogenous RNAs (ceRNAs). NetworkAnalyst was used to construct TF-gene networks and TF-miRNA-gene networks of BICC1 and ceRNA. Furthermore, we investigated the Bicc1 expression in aged Sca-1-positive BMSCs. Result. We detected 923 DEGs and discovered that epidermal growth factor receptor (EGFR) was the top hub gene with a high degree of linkage. According to the findings of the PPI module analysis, EGFR was mostly engaged in cytokine signaling in immune system and inflammation-related signaling pathways. 282 ceRNAs were found to interact with the BICC1 gene. EGFR was not only identified as a hub gene but also as a BICC1-related ceRNA. Then, we predicted 11 common TF-genes and 7 miRNAs between BICC1 and EGFR. Finally, we found that BICC1 mRNA and EGFR mRNA were significantly overexpressed in aged Sca-1-positive BMSCs. Conclusion. As a genetic gene that affects bone mineral density, BICC1 may be a new target for clinical treatment of senile osteoporosis by influencing osteogenic differentiation of BMSCs through EGFR-related signaling. However, the application of the results requires support from more experimental data. [ABSTRACT FROM AUTHOR]

We consider the analysis of an AIDS dataset where each patient is characterized by a list of symptoms and is labeled with one or more TCM syndromes. The task is to build a classifier that maps symptoms to TCM syndromes. We use the minimum reference set-based multiple instance learning (MRS-MIL) method. The method identifies a list of representative symptoms for each syndrome and builds a Gaussian mixture model based on them. The models for all syndromes are then used for classification via Bayes rule. By relying on a subset of key symptoms for classification, MRS-MIL can produce reliable and high quality classification rules even on datasets with small sample size. On the AIDS dataset, it achieves average precision and recall 0.7736 and 0.7111, respectively. Those are superior to results achieved by alternative methods. [ABSTRACT FROM AUTHOR]

Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions via lipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC) as a biomarker of polymyositis and offers new targets to the clinical therapy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of multiple joints, with disruption of joint cartilage. The proliferation of synovial fibroblasts in response to multiple inflammation factors is central to the pathogenesis of rheumatoid arthritis. Our previous studies showed that 4-HNE may induce synovial intrinsic inflammations by activating NF-κB pathways and lead to cell apoptosis. However, the molecular mechanisms of how synovial NF-κB activation is modulated are not fully understood. Here, the present findings demonstrated that 4-HNE may induce synovial intrinsic inflammations by mTORC1 inactivation. While ectopic activation of mTORC1 pathway by the overexpression of Pim-2 may disrupt the initiation of inflammatory reactions and maintain synovial homeostasis, our findings will help to uncover novel signaling pathways between inflammations and oxidative stress in rheumatoid arthritis development and imply that Pim-2/mTORC1 pathway may be critical for the initiation of inflammatory reactions in human rheumatoid arthritis synovial cells. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints. The central pathogenesis of RA is the proliferation of synovial fibroblasts in response to inflammatory cytokines. However, some of the targeted therapies for inflammation reactions do not display significant clinical improvement after initiation of therapy. Thus, the relationship between inflammatory responses and RA therapy is still incompletely understood. In the present study, we proposed to determine whether enhanced inflammations may lead to cell apoptosis in rheumatoid arthritis synoviocytes. Our results indicated that products of lipid peroxidations, 4-HNE, may induce synovial intrinsic inflammations by activating NF-κB pathways and it may lead to cell apoptosis. Pharmacological inhibition of NF-κB activation may reduce the 4-HNE mediated inflammation responses and subsequent cell apoptosis. Our results may help to clarify the role of inflammations on RA development and imply that blocking NF-κB activation may be partly beneficial for human RA therapy. These findings might provide a mechanism-based rationale for developing new strategy to RA clinical therapy. [ABSTRACT FROM AUTHOR]

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations. [ABSTRACT FROM AUTHOR]